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Pharmacokinetics of paclitaxel in an anephric patient
M H Woo1, D Gregornik, P D Shearer
1Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Insights
This study assessed paclitaxel pharmacokinetics in a pediatric patient with recurrent Wilms' tumor undergoing hemodialysis. Paclitaxel exposure was comparable to children with normal kidney function, suggesting similar dosing is feasible.
Area of Science:
- Pharmacology
- Oncology
- Nephrology
Background:
- Recurrent Wilms' tumor poses treatment challenges in pediatric patients.
- An anephric state necessitates careful consideration of drug pharmacokinetics, especially for renally cleared agents.
- Paclitaxel is a chemotherapeutic agent with established efficacy but requires dose adjustment in renal impairment.
Observation:
- Paclitaxel was administered via 24-hour continuous intravenous infusion at doses of 250 mg/m2 and 350 mg/m2.
- Plasma paclitaxel concentrations were analyzed using high-performance liquid chromatography (HPLC).
- Paclitaxel was not detected in the hemodialysis fluid.
Findings:
- Paclitaxel disposition in the anephric pediatric patient was similar to that observed in children with normal renal function.
- Pharmacokinetic modeling revealed a two-compartment model for the lower dose and a saturable elimination model for the higher dose.
- Systemic exposure (AUC) was comparable to or lower than expected for similar doses in patients with normal renal function.
Implications:
- Pediatric patients with renal failure may tolerate paclitaxel treatment using a 24-hour continuous infusion at doses similar to those used in patients with normal renal function.
- Hemodialysis does not appear to significantly clear paclitaxel.
- These findings support the potential use of paclitaxel in anephric pediatric cancer patients, warranting further investigation.
Purpose:
To assess the pharmacokinetics of paclitaxel for recurrent Wilms' tumor in an anephric pediatric patient receiving hemodialysis.
Methods:
Paclitaxel was administered at a dose of 250 mg/m2 and 350 mg/m2 by 24-h continuous intravenous (IV) infusion as two consecutive courses, respectively, separated by approximately 3 weeks. Paclitaxel plasma concentrations were measured by high-performance liquid chromatography (HPLC).
Results:
Paclitaxel disposition was comparable to that reported in similarly treated children with normal renal function. For the first course (250 mg/ m2), paclitaxel concentrations were best fit by a two-compartment, first-order model. The calculated pharmacokinetic parameters were 0.312 h(-1) for the first-order rate constant of elimination (Ke), 52.4 l/m2 for the apparent volume of distribution (Vc), 0.170 h(-1) and 0.105 h(-1) for the first-order rate constants for transit from central to peripheral compartments (Kcp) and peripheral to central compartments (Kpc), respectively, 16.9 microM x h for the area under the plasma concentration-versus-time curve (AUC), and 273 ml/min per m2 for average clearance (Cl). The concentration-versus-time data with the second course (at the higher dosage of 350 mg/m2) were better described by a two-compartment model with saturable elimination. The calculated pharmacokinetic parameters were 12.0 micromol x h(-1) for the maximal rate of elimination (Vm1-0), 0.158 microM for the concentration at which the rate of elimination is 50% of maximal (Km1-0), 0.809 h(-1) for Kcp, 0.0792 h(-1) for Kpc, 23.5 l/m2 for Vc, 20.9 microM x h for AUC, and 327 ml/min per m2 for Cl. Paclitaxel was undetectable in the dialysate.
Conclusions:
The level of systemic exposure in our anephric patient was comparable to or lower than that achieved in patients with normal renal function at similar dosages. The patient tolerated therapy without problems. It appears that pediatric patients in renal failure can be treated with paclitaxel as a 24-h continuous infusion at doses similar to those used in patients with normal renal function.